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BACKGROUND: The role of bisphosphonates (BP) in hypertrophic osteoarthropathy (HPOA) is unclear. We presented a case of primary HPOA and performed a systematic review of literature on the effect of BP on treatment response in primary and secondary HPOA.
METHODS: The study was prospectively registered in PROSPERO (CRD42022343786). We performed a PubMed literature search that restricted to the English language. We included patients diagnosed with primary or secondary HPOA who received BP. The primary endpoint assessed was the effectiveness of BP on response to pain or arthritis. Secondary outcomes included timing, degree, and duration of response, comparison to other HPOA therapies, impact of BP on radiology, bone scan, bone turnover markers, and adverse effects of BP.
RESULTS: Literature search retrieved only case reports. Forty-five patients (21 primary, 24 secondary HPOA) had received BP. Majority(88.3%) experienced improvement in pain or arthritis. Response was gradual for primary HPOA and within a median of 3 to 7 days for secondary HPOA after treatment with BP. Most patients had reduced bone scan uptake after BP. When other HPOA therapies were tried, half responded to BP after not having previously responded to other therapies, while a third received the treatments concurrently, making it difficult to attribute treatment response to a drug. Reporting of other secondary outcomes was very heterogenous and qualitative to draw conclusions. No major adverse effects have been reported for BP in HPOA.
CONCLUSIONS: Bisphosphonates provide an effective and safe treatment option for primary and secondary HPOA. However, there is a lack of randomized controlled trials.

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OBJECTIVE: This study aims to provide a detailed evaluation of a case of secondary hypertrophic osteoarthropathy (HOA) and to explore insights into the presence and consequences of disease in medieval rural Italy.
METHODS: The skeleton of a male (US 4405) with an estimated age at death of 51-69 years excavated from the medieval rural site of Pieve di Pava (Siena, Italy).
METHODS: Macroscopic and radiological (x-ray, CT) analyses were performed.
RESULTS: Symmetrical extensive periosteal new bone formation on the diaphyseal and metaphyseal regions of this individual\'s long bones; the lower limbs were more extensively and severely affected than the upper limbs and the distal segments were more severely altered in comparison to the proximal ones.
CONCLUSIONS: The macroscopic and radiological features are highly consistent with a diagnosis of secondary HOA.
CONCLUSIONS: The excellent state of preservation allowed the evaluation of rarely noted skeletal manifestations of HOA and provided insight into aspects of rural life in medieval Italy.
CONCLUSIONS: Molecular analysis was not successful in sequencing the aDNA of tuberculosis, therefore the underlying primary cause of secondary HOA, whether pulmonary or extrapulmonary, remains obscure in this case.
UNASSIGNED: It is advisable to regularly revisit the data available from osteoarchaeological collections in order to identify further cases of HOA, along with to further investigate the known cases to search for the underlying primary disease.

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Hypertrophic pulmonary osteoarthropathy(HPO)is a tumor-associated syndrome that features the triad of clubbed fingers, periosteal bone growth in long bones, and arthritis, and is often associated with an adenocarcinoma or squamous cell carcinoma. This report presents details of a case of HPO associated with pleomorphic carcinoma, which was relieved by treatment. A 47-year-old woman was presented with a complaint of generalized arthralgia. A physical examination showed swollen joints in the body and clubbed fingers. Chest CT revealed a mass shadow in the left upper lobe and ultrasound- guided biopsy findings led to a diagnosis of non-small cell lung cancer. Furthermore, bone scintigraphy indicated symmetrical accumulation in bones and joints throughout the body. A right upper lobectomy was performed along with combined chest wall resection and mediastinal lymph node dissection with an open chest, and the presence of lung cancer complicated with HPO was indicated. Pathological examination results revealed a diagnosis of pleomorphic carcinoma(pT4N0M0, Stage ⅢA). Systemic arthralgia was resolved on the first postoperative day. One year after surgery, a solitary brain metastasis developed and was removed, with no recurrence at the time of writing. Joint symptoms related to HPO can be expected to improve with treatment of pulmonary lesions, thus aggressive procedures for diagnosis and treatment are desirable.

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In 2015 a surprising find of human bone fragments from a child was made in a collection of the Egyptian Museum and Papyrus Collection, Berlin. These bone fragments from Southern Egypt date to 3400-3300 BC and represent the distal parts of both femora and the proximal parts of both tibiae (bones around the knee joint). The bones have a specific appearance, probably indicating a systemic disease. Due to the incomplete state of the skeletal remains, the distribution of the lesions throughout the entire skeleton could not be observed, thus preventing a better diagnosis of the underlying pathological process. The poor collagen preservation of the bone precluded aDNA testing for pathogens. The bone fragments were instead subjected to radiographic and microscopic analysis which revealed a recurrent periosteal process accompanied by a distinct osteoclastic component. A possible diagnosis might be an underlying unknown pathological process, leading to the development of a secondary Hypertrophic Osteoarthropathy (HOA).